rs10888838

Variant names:

• chr1-54207424-C-T
• rs10888838
• NM_016491.4:c.646+2014C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330602.1(MRPL37):​c.646+2014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,096 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2244 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL37 NM_001330602.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 16 publications found

Genes affected

MRPL37 (HGNC:14034): (mitochondrial ribosomal protein L37) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330602.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL37	NM_016491.4	MANE Select	c.646+2014C>T		intron	N/A	NP_057575.2
	MRPL37	NM_001330602.1		c.646+2014C>T		intron	N/A	NP_001317531.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL37	ENST00000360840.9	TSL:1 MANE Select	c.646+2014C>T		intron	N/A	ENSP00000354086.5
	MRPL37	ENST00000336230.10	TSL:1	c.256-2524C>T		intron	N/A	ENSP00000338526.6
	MRPL37	ENST00000605337.5	TSL:5	c.646+2014C>T		intron	N/A	ENSP00000473980.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23304 AN: 151976 Hom.: 2239 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.153 AC: 23317 AN: 152096 Hom.: 2244 Cov.: 32 AF XY: 0.160 AC XY: 11872 AN XY: 74340

African (AFR) AF: 0.0977 AC: 4054 AN: 41492

American (AMR) AF: 0.189 AC: 2889 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 394 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2433 AN: 5160

South Asian (SAS) AF: 0.264 AC: 1274 AN: 4824

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10566

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10017 AN: 67982

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.147 Hom.: 2917

Bravo AF: 0.152

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10888838; hg19: chr1-54673097;